Cadmium is a widely dispersed toxic trace metal. In recent years, research has documented a cardiotoxic effect of this metal at relatively low levels of exposure. The mechanism of this cardiotoxicity has been shown to involve peroxidative tissue injury secondary to a reduction in the activities of the selenium-containing enzyme, glutathione peroxidase, and the copper-containing enzyme, superoxide dismutase. The purpose of this proposal is to define, quantitatively, the contributions of glutathione peroxidase and superoxide dismutase in preventing or ameliorating cadmium-induced lipid peroxidation in the heart. Since the current regulatory standards for non-occupational exposure to cadmium are based on the kidney being the target organ, and since several reports suggest that cadmium cardiotoxicity may occur in the absence or renal damage, this proposal will also examine the kidney of treated rats to establish the basis for the apparently greater vulnerability of the heart over the kidney to cadmium toxicity. The role of metallothionein in mediating renal toxicity will also be examined.